Pediatric obesity

Prepared by : Farah El Soheil
Presented to: Dr. Nour Chamsine

Lebanese International University
School of Pharmacy
Advanced Pharmacy Practice Experience
Pediatric Intensive Care Unit
Pediatric Obesity:
Causes, Consequences and Intervention Approaches
Dec 20, 2019

i. Introduction
ii. Definitions
iii. Epidemiology
iv. Classification criteria
v. Etiology
vi. Complications
vii. Pathophysiology
viii. Risk Factors
ix. Complications
x. Management
i. Non-pharmacologic
ii. Pharmacologic
iii. Surgical
xi. Prevention
xii. Future Promising Drugs
xiii. Conclusion
OUTLINE
3

INTRODUCTION
A growing number of
youth suffer from
obesity & in particular
severe obesity for
which intensive
lifestyle intervention
doesn’t adequately
reduce excess
adiposity
GBD 2015 Obesity Collaborators , et al. (n.d.). Health Effects of Overweight and Obesity in 195 Countries over 25 Years. - PubMed - NCBI. Retrieved from
https://www.ncbi.nlm.nih.gov/pubmed?term=28604169
4

Excess
accumulation of
body fat
Varies with the
parameter used
for measuring
Weight to age
• For children ≤ 2
years old
Body mass index
(Quetelet index)
• For children ≥ 2
years old
DEFINITIONS
5
Obese
• BMI ≥ 30 Kg/m2
• ≥ 95% percentile
Overweight
• BMI : 25-30 Kg/m2
• 85-95% percentile
Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449849/
Severly Obese
• BMI ≥ 35 Kg/m2
• ≥ 120% of 95 percentile
Obese
• >97.7th percentile

Percentile <5: Underweight
Percentile ≥5 and <85: Healthy weight
Percentile ≥85 and <95: Overweight
Percentile ≥95: Obesity
CDC GROWTH CHART: BOYS
6
UpToDate. (n.d.). Retrieved from https://www.uptodate.com/contents/management-of-childhood-obesity-in-the-primary-care-
setting?search=pediatric%20obesity&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4

CDC GROWTH CHART: GIRLS
Percentile <5: Underweight
Percentile ≥5 and <85: Healthy weight
Percentile ≥85 and <95: Overweight
Percentile ≥95: Obesity
7

EPIDEMIOLOGY
8
32 million
in 1990
42 million
in 2013
70 million
expected
in 2025
Global obesity in
children 0-5 years old
Class 2 obesity is
increasing
significantly in
girls of all ages &
in boys between 12
and 19 years of age
Skinner AC, Perrin EM, Moss LA, Skelton JA. Cardiometabolic risks and severity of obesity in children and young adults. N Engl J Med. 2015;373:1307–1317

 Primary/ Constitutional:
 No secondary cause
 Secondary/ organic/ exogenous:
 Genetic syndromes: prader willi, down’s, bradet-biedl, cohen, carpenter
 Hypothalamic: infectious ( TBM, post meningetic sequelae, ICSOL,
radiation, surgery, head trauma, hypothalamic hamartoma)
 Endocrine: cushing, hypothyroidism, pseudohypoparathyroidism, PCOS
 Drugs
 Psychological: bulimia nervosa, depression
 Handicapped: sedentary lifestyle
9
CLASSIFICATION

 Short stature
 Mental retardation
 Hypogonadism
 Hypotonia
 Failure to thrive
10
PRADER WILLI

 Retinal degeneration
 Mental retardation
 Renal dysplasia
 Short stature
 Hypogonadism
11
LAURENCE MOON
BARDET BIEDL SYNDROME

12
OTHER GENETIC DISEASES
Carpenter Syndrome

13
PATHOPHYSIOLOGY

RISK FACTORS
14
Food advertising
aimed at children
Large portion
size
Overconsumption of sugar
sweetened beverages
Declines in overall physical
activity before and after
school hours
Increased availability of low
cost high calorie refined
grains and added sugar
Community environments
that inhibit active living
Increased screen time
Others:
• Obesity in one or both
parents
• Infants of diabetic
mothers
• Formula feeding during
infancy
• Medications:
antipsychotics, steroids,
antiepileptics
Higher birth weight & rapid
growth during infancy

COMPLICATIONS
15
MUSCULOSKELETAL
RENAL
GASTROINTESTINAL
PULMONARY
PSYCHOSOCIAL NEUROLOGICAL
CARDIOVASCULAR
ENDOCRINE
HERNIA
DVT/PE
Stress incontinence
Risk of GYN malignancy

16
TREATMENT APPROACH
Pediatric Obesity'Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline. (1, March). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283429/figure/F1/

• Birth weight
• Pattern of weight gain
• Family history
• Medications
• Menstrual history
• Development
assessment
EVALUATION
17
Take
history
Evaluation

• General & systemic
examination
• Anthropometry
• Blood pressure
• Acanthosis nigricans
• Acne,hirsutism, hairfall
• Dysmorphic facies
• Pubertal status
• Psychiatric evaluation
EVALUATION
18
Physical
Examination
Evaluation
Cont’d

• Lipid profile
• Glucose tolerance test
• Thyroid function
• Gonadal axis- LH FSH
testosterone
• Bone age assessment
• Growth hromone
• Vitamine D
• Serum insulin, HBA1C
EVALUATION
19
Investigations
Evaluation
Cont’d

Management Non-
pharmacologic
20

Nutritional factor Contribution to weight gain Examples of goals*
Restaurants and fast food
Fast food meals increase portion
size and total energy intake and are
of poorer nutrient quality
1 or fewer take-out or fast-food
meals weekly
Sweetened beverages
High intake of sugar-sweetened
beverages is linked to increased
prevalence of obesity in children
Fruit juice is also considered a
sweetened beverage
Avoid all sugar-sweetened
beverages and juice
Portion sizes
Larger portions lead to increased
energy intake
Goals depend on
• Child's age
• Degree of obesity
• Level of physical activity
NUTRITION GOALS
21

Energy-dense foods
An association between energy-dense
foods and obesity is not yet established
in children
Avoid fried foods
Eliminate high-calorie snacks
Limit amount of cheese & high fat milk
Choose cereals with low sugar content
Fruits and vegetables
Fruits and vegetables displace energy-
dense foods and increase satiety
At least 5 servings of vegetables and
fruits daily
Breakfast
Skipping breakfast is associated with
increasing obesity in children
Moderate breakfast daily
Avoid high sugar breakfasts
Meal frequency and snacking
Snacking increases energy intake and
poorer diet quality
Offer 3 meals daily on a regular
schedule
1 or 2 additional healthy snacks
NUTRITION GOALS
Cont’d
22

 First line therapy for obese pediatric patients
 Dietary: Of total calories:
 Carbohydrates: 45-65%
 Proteins: 10-20%
 Fats: 30-40%
 Weight Monitoring:
 ≤11 years: 0.5 Kg/month
 > 11 years: 1 Kg/month
NON PHARMACOLOGICAL MEASURES
23
Sci-Hub | Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity. Obesity, 27(2), 190–204 | 10.1002/oby.22385. (n.d.).
Retrieved from https://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/30677262/

 Lifestyle& Physical Activity:
 No TV for children < 2 years
 ½ to 1 hour of outdoor daily activity
 No more than 2 hours of TV for children > 2 years
 60 minutes of vigorous exercise daily
 Keep safe, interesting and practical
24
Sci-Hub | Clinical Considerations Regarding the Use of Obesity Pharmacotherapy in Adolescents with Obesity. Obesity, 27(2), 190–204 | 10.1002/oby.22385. (n.d.). Retrieved from https://sci-
hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/30677262/
Cont’d

 Behavioral therapy:
 Parental motivation & commitment
 No stacking of unhealthy food in house
 Setting realistic goals for exercise
 Timely monitoring
25
Cont’d

There are currently
only two available
FDA-approved anti-
obesity medications
with pediatric
indications
• Orlistat approved for age
≥12 years
• Phentermine for age >16
years
The safety and long-
term efficacy of other
adult FDA approved
agents are
questionable
• Liraglutide 3.0 mg
• Naltrexone SR/bupropion
SR
• Lorcaserin
• Phentermine/topiramate
extended-release
combination
PHARMACOLOGIC MEASURES
27
Use of Lisdexamfetamine to Treat Obesity in an Adolescent with Severe Obesity and Binge Eating. (n.d.). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406487/
For
Severe
Obesity

There are no medications
approved for binge eating
disorder in children
Lisdexamfetamine
Recently received FDA
approval for the treatment of
binge eating disorder in
adults
Is approved for the long-
term treatment of ADHD in
children and adolescents
ages 6–17 years
PHARMACOLOGIC MEASURES
28
Cont’d

Pancreatic and gastric lipase inhibitor
Obesity ≥12 years of age
Recommened dose 120mg three times daily with meals
Flatulence, oily spotty stools, diarrhea, fat soluble vitamins/ mineral
deficiency
Chronic malabsorption syndrome, cholestasis
Reduced BMI by 0.5 to 4 kg/m(2)
Reduced fat absorption by 30% with limited cardiometabolic effects
29
ORLISTAT
Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 2005;293:2873-2883.
Reevaluate if the
patient doesn’t have a
.4% BMI reduction
after 12 weeks

Amphetamine like catecholaminergic & dopaminnergic stimulant
Obesity >16 years of age for “short term”
Phentermine/ topiramate ER approved for long-term use in adults
<16 years old or for long term use
Increases heart rate & blood pressure
Dry mouth, insomnia, constipation, anxiety, irritability
Cardiovascular disease hyperthyroidism, glaucoma, agitated states
BMI reduction of 4.1% at 6 months
30
PHENTERAMINE
Ryder JR, Kaizer A, Rudser KD, Gross A, Kelly AS, Fox CK. Effect of phentermine on weight reduction in a pediatric weight management clinic. Int J Obes (Lond) 2017;41:90-93.

Activation of protein kinase pathway & inhibition of ghrelin
secretion
≥10 years of age for type 2 diabetes mellitus
PCOS, insulin resistance, metabolic syndrome,
antipsychoticmedication-induced weight gain, stress
eating/emotional eating
Bloating, diarrhea, flatulence, B12 deficiency
Lactic acidosis & elevation in liver enzymes is not noted
Hold 48 hours prior to contrast; lactic acidosis
Limited BMI reduction 1.16% in 6-12 months
Decreased odds of developing DMII
31
METFORMIN
O’Connor EA, Evans CV, Burda BU, Walsh ES, Eder M, Lozano P. Screening for obesity and intervention for weight management in children and adolescents:
evidence report and systematic review for the US Preventive Services Task Force. JAMA 2017;317:2427-2444.

Modulation of various neurotransmitters including gamma
aminobutyrate
Epilepsy >2 years of age and migraines >12 years of age
Phentermine/ topiramate ER approved for long-term treatment of
obesity in adults
Weight loss in adult and pediatric patients; useful adjunct in binge
eating disorders and weight regain post bariatric surgery
Cognitive dysfunction, kidney stones, metabolic acidosis; teratogenic:
decreased efficacy of oral contraceptives
Inborn errors of metabolism with hyperammonia and encephalopathy,
acute myopia and secondary angle-closure glaucoma; neuropsychiatric
dysfunction, metabolic acidosis
BMI reduction of 4.9% on topiramate 75 mg daily for at least 3 months
32
TOPIRAMATE
Fox CK, Marlatt KL, Rudser KD, Kelly AS. Topiramate for weight reduction in adolescents with severe obesity. Clin Pediatr (Phila) 2015;54:19-24.

GLP-1 agonist in the hypothalamus & an appetite
suppressant
Type 2 diabetes mellitus in adults
<18 years of age for obesity (polygenic with presence of
diabetes, hypothalamic syndrome)
Bloating, nausea/vomiting, abdominal pain, elevation of
pancreatic amylase and lipase
Postmarketing reports: pancreatitis, renal impairment,
severe GI disease
BMI reduction of 3.42% at 3 months
33
EXENATIDE
Kelly AS, Metzig AM, Rudser KD, et al. Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study. Obesity (Silver
Spring) 2012;20:364-370.

Central nervous system stimulant
Age ≥6 years of age for ADHD
Short-term use of binge eating disorder in adults
For younger children with ADHD and obesity or binge eating disorder
Anorexia, anxiety, weight loss, diarrhea, dizziness, dry mouth,
irritability, insomnia,N&V, upper abdominal pain
Blood pressure and heart rate increases; psychiatric disorders;
suppression of growth; peripheral vasculopathy, SSRI with
serotonergic agents
In 6- to 12-year-old age group, 2.5 lb with 70-mg dose over 4 weeks
In 13- to 17-year-old age group, 4.8 lb with 70-mg dose over 4 weeks
34
LISDEXAMFETAMINE
Vyvanse (lisdexamfetamine dimesylate) [package insert]. Lexington, MA: Shire US; 2017

GLP-1 agonist
Saxenda 3 mg approved for obesity in adults
Victoza approved for type 2 diabetes in adults
<18 years of age
Abdominal pain, nausea, vomiting, diarrhea, potential
hypoglycemia
Postmarketing reports: pancreatitis, renal impairment,
severe GI disease
35
LIRAGLUTIDE
. Danne T, Biester T, Kapitzke K, et al. Liraglutide in an adolescent population with obesity: a randomized, double-blind, placebo-controlled 5-week trial to assess safety,
tolerability, and pharmacokinetics of liraglutide in adolescents aged 12–17 years. J Pediatr 2017;181:e143. doi:10.1016/j.jpeds.2016.10.076

Not FDA approved for
the treatment of obesity
GH treatment of
children and
adolescents with Prader-
Willi syndrome,
particularly when
started early
Decreases body fat
percentage
Increases lean body
mass
Sustains effects for the
long term
36
GROWTH HORMONE OCTREOTIDE
Carrel AL, Myers SE, Whitman BY, Allen DB. Benefits of longterm GH therapy in Prader-Willi syndrome: a 4-year study. J Clin Endocrinol Metab. 2002;87:1581–1585.

• Extreme obesity and comorbidities
persist despite compliance with a formal
program of lifestyle modification
• Psychosocially stable
• Patient demonstration of the ability to
adhere to diet
• There is access to an experienced
surgeon
• BMI ≥ 50kg/m2 or ≥ 40kg/m2 +
comorbidities
• Adolescent or older
Indications Techniques
SURGICAL MEASURES
38

Exclusive
breast
feeding
Timely
complementary
feeding
Healthy
feeding
practices
Fiber in diet=
age+ 5g
No fat
restriction
to be done
before 2
years of
age
For children ≥2
years, fat contributes
20-30% to calories
PREVENTION
39

CNS amphetamine compound with high potential for abuse and
dependence
• FDA-approved for ADHD in children/adolescents and BED in adults
Serious cardiovascular reactions such as sudden death, average
height decline of ~2 cm over 12 months and 2.7 kg less growth in
weight over 2 years, anorexia, anxiety, weight loss , diarrhea,
dizziness, dry mouth, irritability, insomnia,N,V & abdominal pain
Blood pressure, heart rate, depression exacerbation or mood
changes & growth in children
40
FUTURE PROMISING DRUGS

Melanocortin 4 receptor agonist,
pending FDA approval for monogenic
obesity in adults & pediatrics
Dry mouth mild induration at injection
site, darkening of skin nevi
Blood pressure, heart rate in structural
heart disease
41
FUTURE PROMISING DRUGS
Kuhnen P, Clement K, Wiegand S, et al. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N Engl J Med 2016;375:240-246.
Cont’d

 Lifestyle interventions remain the treatment of choice in pediatric
obesity
 Concomitant pharmacotherapy may be beneficial in some patients
 Orlistat should be considered as second-line therapy for pediatric
obesity
 Evidence suggests that other diabetes and antiepileptic
medications may also provide weight-loss benefits, but safety
should be further evaluated
42
CONCLUSION

Pediatric obesity

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